Dr. Longenecker is a cardiologist with a special interest in cardiovascular disease among people with HIV infection. Perhaps best known in the HIV community for his research on rosuvastatin in the SATURN-HIV trial, he works on more than a dozen research projects on cardiovascular disease and HIV infection in the United States and Uganda. Dr. Longenecker also conducts population-based research with an eye toward strengthening healthcare systems. With a medical degree from Ohio State University College of Medicine, he completed a residency in internal medicine at the University of California, San Francisco and a cardiology fellowship at Case Western Reserve University School of Medicine in Cleveland.

Mascolini: When should people with HIV be tested for dyslipidemia?

Longenecker: I think all patients with HIV need to be tested for dyslipidemia. Certainly HIV patients should be tested before starting antiretroviral therapy, then again after starting therapy because of the effects that some antiretrovirals can have. We know that uncontrolled HIV infection itself can cause lipid problems before starting ART. The chronic inflammation and immune activation that result from HIV infection can cause low HDL cholesterol and high triglycerides even before starting ART.1,2 So it's important to know those pretreatment levels and how they change with therapy. I would also add that the age and overall cardiovascular risk profile of a patient will determine when you start checking lipid panels: Older people with more cardiovascular risk will require more frequent monitoring.

Mascolini: For a 50-year-old without a lot of cardiovascular risk, once they start ART, how often would you recheck lipids?

Longenecker: You're going to get a sense of what antiretroviral therapy is doing to their lipids within the first 6 months or so. So it's reasonable to check within that time frame. For someone who's 50 years old, even without many cardiovascular risk factors, they may be close to having an indication for starting a statin. For someone who's on a statin, it's reasonable to check once initially 3 months after they start the statin then once a year thereafter. For someone who's younger, you won't have to check that often.

Lipid levels are determined primarily by the interaction of your genetics with your environment -- in other words, your diet and exercise plus medications including ART. One's genes obviously don't change, but if someone's diet and exercise pattern don't change, you wouldn't necessarily expect their lipid panel to change that much.

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Practical Approaches to Diet and Exercise

Mascolini: What's the most important lipid-altering lifestyle change HIV clinicians should encourage?

Longenecker: This is a very important question. One of the cornerstones of lipid management in anybody is diet and lifestyle change. I think the most important thing is to emphasize moderation in diet and considering what we call the Mediterranean diet:3 lots of healthy plant oils, fish oils, plenty of dietary fiber, and less saturated fat and animal fat.

I think extreme diets are not particularly helpful for managing lipids. The best approach is moderation -- a dietary pattern that somebody can sustain over time -- rather than going on a rigid diet for a time then bouncing back to the opposite extreme. Also, we know that sugary drinks are bad for cardiovascular health and can potentially have an adverse effect on lipids. So that's one thing we can really target -- trying to reduce consumption of sugary drinks.

Combining exercise with a practical diet is also important. Exercise increases HDL cholesterol. Low HDL cholesterol is one of the hallmarks of HIV infection, and exercise can improve that. I really stress exercise with my patients. I think exercise will have much smaller effects on other lipids, but because of the exercise-induced cardiovascular risk reduction that goes beyond any effects on lipids, exercise is something that's very important to stress with our patients.

Mascolini: Have you had luck in getting your HIV patients to be more physically active? What seems to work for most people?

Longenecker: We deal with a challenging population here at University Hospitals in Cleveland. We're on the border with East Cleveland, so we have many patients of low socioeconomic status who live in "food deserts" where it's difficult to get healthy food. Sometimes it's difficult for them to exercise safely outside, and it's cold during the winter. So the HIV population here in Cleveland faces several healthy-lifestyle challenges.

Nevertheless, we work with people where they're at. And many of our patients can do beneficial exercises inside their apartments, such as strength training and yoga. Such exercise is not going to have much of an effect on their lipids, but it could be a good place to start. We also encourage incorporating exercise into their daily lives by walking, maybe parking farther out in the parking lot if they're going to the grocery store or walking up flights of stairs rather than taking the elevator.

We have a program here run by one of the nursing faculty called System Change that aims to help our HIV patients develop ways to change their environment so they make healthy choices more automatically and don't have to rely on motivation to make a healthy choice. An example would be putting sugary drinks in the back of the refrigerator, behind more healthy options like a bottle of water. Or putting a note in the stairwell of your office encouraging you to take the stairs rather than take the elevator. Our patients do little experiments with themselves and report back to the group to share what's worked for them.

One of the things I'd like to stress about the HIV community in HIV clinics around the country is the strong sense of camaraderie. People identify with other people who have HIV, and getting HIV-positive people together in groups is a good thing. In our clinics we've run exercise groups, walking groups, yoga groups, that sort of thing. These groups help people at least take the first step to develop a healthy lifestyle.

We also have a community garden behind the clinic. Because there are many "food deserts" here in Cleveland, our patients can grow vegetables in these gardens then harvest some of the vegetables to use in their cooking. That has been a healthy thing for the patients, but also a community-building exercise. The bonds created by these types of group activities are something our HIV clinics should aim to foster.

Impact of HCV, TDF-to-TAF Switch, and Switching ART

Mascolini: Several studies found better lipid profiles with HCV/HIV coinfection than with HIV alone.4-7 Do these findings affect how clinicians should manage lipids in coinfected people?

Longenecker: We know that HCV infection is typically associated with lower LDL cholesterol, which has to do with how HCV affects the liver. But it's important to recognize that patients with hepatitis C infection are at increased risk of atherosclerotic vascular events, and people with HCV/HIV coinfection may be at higher risk than people with HIV monoinfection.8,9 Because of this higher cardiovascular disease risk, I think it's important to have different lipid targets with HCV-infected patients. Often we would prescribe a statin for an HCV-infected person to reduce cardiovascular risk, even if the lipid profile is not as abnormal as it is for other patients.

A general principle of cardiovascular risk reduction is that you want to treat patients who are at higher absolute risk regardless of what their lipids are because we know that the relative risk reduction with statins is consistent across all lipid levels. It's just that patients with lower lipid levels tend to have lower risk, so the absolute statin benefit may be less.

Mascolini: Tenofovir disoproxil fumarate (TDF) has a beneficial effect on lipids not seen with tenofovir alafenamide (TAF).10,11 As people switch from TDF to TAF regimens, should clinicians watch lipids more closely after people start TAF?

Longenecker: This issue is on the margins of clinically relevant, because the lipid differences between TDF and TAF are subtle. In the end it's going to be relatively uncommon that switching somebody from TDF to TAF puts them at a risk level that makes you recommend a statin. Our patients' cardiovascular risk profile is driven by many factors -- including smoking, hypertension, diabetes, age, race, and gender -- that are unrelated to lipids. So a minor change in LDL cholesterol really is not going to be that clinically relevant overall.

In a patient with familial hypercholesterolemia or a very bad lipid profile to start, the switch to TAF may be clinically relevant, so you have to evaluate the impact of switching TDF to TAF on a case-by-case basis. But overall that switch will not matter.

Mascolini: If a patient has taken a suppressive but dyslipidemic antiretroviral regimen for years, should the clinician stick with that regimen and treat the abnormal lipids or consider switching to a newer regimen?

Longenecker: Great question and one that is discussed a lot. I think it depends entirely on the patient-provider discussion about this. We know that switching antiretroviral regimens is associated with a small but quantifiable risk of virologic failure. So if an antiretroviral regimen is working for somebody and you can easily treat their lipids with a statin or other drugs -- and they don't seem to be at particularly high risk and they're not difficult to treat -- then I think it's fine to continue the antiretrovirals.

In situations where, for example, a person with very difficult-to-treat hypertriglyceridemia is taking a lipogenic protease inhibitor, it may be reasonable to try switching to something else. But that discussion must be had between the provider and the patient, because often the patient will feel very strongly about what to do.

Mascolini: Is there a typical abnormal lipid profile in people with HIV?

If someone has high triglycerides it's very important to get them to quit drinking heavily, and if they have diabetes we should try to get their hemoglobin A1c better controlled.

Longenecker: One of the hallmarks of dyslipidemia in HIV is the phenomenon of low HDL with high triglycerides. We see this in other chronic inflammatory diseases and in metabolic diseases. In the metabolic syndrome, for example, two of the criteria are low HDL and high triglycerides. This is a very proatherogenic lipid profile. So regardless of what the LDL cholesterol is, if you have low HDL and high triglycerides, this will increase the amount of atherogenic lipid particles. For any given LDL cholesterol level, there will be more LDL particles that can cause disease.

It's nice to see that over the years, as antiretroviral therapy has improved and we've started treating people at higher CD4 counts, we've seen less of this low HDL/high triglyceride phenomenon. That is really encouraging and it makes lipid management a lot easier now than it was 15 years ago.

But occasionally I do see a patient with very high triglycerides and I think it's important to address factors besides just giving them lipid drugs -- the two most important factors being diabetes and alcohol use. Both diabetes and heavy drinking can make the triglycerides go way out of whack. If someone has high triglycerides it's very important to get them to quit drinking heavily, and if they have diabetes we should try to get their hemoglobin A1c better controlled. Then you can add a fibrate, fish oil, or niacin, but it's important to address the diabetes or drinking first.

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